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Neuregulin 1 type III (Nrg1III) overexpression worsens the radial sorting defects of Lama2−/− mice.

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posted on 21.06.2017, 17:24 by Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri

(A) Transverse semithin sections of sciatic nerves from mice of the indicated genotypes at postnatal day 16 (P16) are shown. Nrg1IIItg//Lama2−/− mice have more bundles of naked axons (unsorted bundles) than Lama2−/− mice (arrowheads). (B) Electron micrograph analysis shows that in Lama2−/− and Nrg1III+/−//Lama2−/− nerves these unsorted bundles contain amyelinated, naked axons with diameter >1 μm (asterisk), while in wild-type (WT) and Nrg1IIItg nerves, there are only Remak bundles that contain axons ensheathed and smaller than 1 μm (arrow). (C) Number of unsorted bundles per nerve cross semithin section, showing a 3-fold increase in the number of unsorted bundles in Nrg1IIItg//Lama2−/− (106.33 ± 5.7 versus 35.33 ± 0.5 Lama2−/− ***p = 0.0005 by Student t test; n = 3). (C’): The number of Remak bundles on ultrathin electron microscopy (EM) sections is decreased in Nrg1IIItg//Lama2−/− and Lama2−/− mutants (***p = 0.001 by 1-way ANOVA with Bonferroni multiple comparison test, n = 4). (C”): All mutant nerves have reduced numbers of axons in Remak bundles on ultrathin EM sections (**p = 0.005; ***p = 0.001 by 1-way ANOVA with Bonferroni multiple comparison test, n = 4). (D) Examples of precocious myelination of axons that have not been sorted into a 1:1 relationship (arrows). Bar = 10 μm in A, 2 μm in B and D. The numerical data used in C–C” are included in S1 Data.